SS ection

Office of Energetics

Recruitment actively underway for •post-doctoral fellows •research track faculty •tenure track faculty David B. Allison, Ph.D.

Why Study Energy Balance and How?

Disclosure

I have received financial and other benefits from the following entities: the Frontiers Foundation; The Federal Trade Commission; Vivus, Inc; Kraft Foods; University of Wisconsin; University of Arizona; Paul, Weiss, Wharton & Garrison LLP; Sage Publications, and additional government, non-profit and for profit organizations with interests in obesity, nutrition, and health.

Outline

1. Why do we even need to study EB?

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

Diana Thomas’ Software

If we controlled all the obvious factors, we would control weight to within trivial differences, right?

Miller RA, Harrison DE, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Strong R. An Aging Interventions Testing Program: study design and interim report. Aging Cell. 2007 Aug;6(4):565-75. Epub 2007 Jun 18.

What if we all just ate

a little bit

less?

2.0

1.0

0.0

6.0

5.0

4.0

3.0

95% food Ad libitum P=0.0307

*

P=0.0121

*

0 1 Weeks 2

*

P=0.0050

3 7.5

5.0

2.5

0.0

20.0

17.5

15.0

12.5

10.0

0 95% food Ad libitum P=0.0582

**

P=0.0060

**

1 Weeks 2 3

Mild calorie restriction induces fat accumulation in female C57BL/6J mice.

Li X, Cope MB, Johnson MS, Smith DL Jr, Nagy TR.

Obesity (Silver Spring). 2010 Mar;18(3):456-62.

What if we all just ate

a lot

less?

[40% DR]

Liao CY, Rikke BA, Johnson TE, Gelfond JA, Diaz V, Nelson JF. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell. 2011 Aug;10(4):629-39.

How about Primates?

A rapidly occurring compensatory decrease in physical activity counteracts diet-induced weight loss in female monkeys.

“18 adult ovariectomized female monkeys were placed on a low-fat diet, and available calories were reduced by 30% compared with baseline consumption for 1 mo.

Surprisingly, there was not significant weight loss.”

Am J Physiol Regul Integr Comp Physiol. 2010, Apr; 298(4):R1068-74.

How about Great Apes (Homo Sapiens)?

Mandatory food supplementati on studies:

Preliminary unpublished data

.

Energy Compensation Within a Day

Based on CSFII data.

250 200 150 100 50 0 Difference in Meal Energy Intake Difference in Day Energy Intake

Anderson, Michael and David A Matsa. 2011. Are Restaurants Really Supersizing America?. American Economic Journal: Applied Economics. 3(1): 152-188.

Compensation is Sometimes Cognitively Mediated

C. Werle, B. Wansink, C. Payne. Just thinking about exercise makes me serve more food . Physical activity and calorie compensation. Appetite, 56, Issue 2, April 2011, Pages 332-335 .

Results …indicate that simply reading about physical activity leads participants to compensate by serving themselves more snacks.

Sometimes we do not consider the unstated and

completely opposite

implicit assumptions :

• • Warning away from restaurants –

Implicit Assumption is undercompensation.

Advocacy of Breakfast

– Implicit assumption is overcompensation.

Does Eating Breakfast Promote Weight Loss?

Schlundt et al. The role of breakfast in the treatment of obesity: a randomized clinical trial. Am J Clin Nutr 1992 Mar;55(3):645-51 Fifty-two moderately obese adult women were stratified according to their baseline breakfast-eating habits and randomly assigned a weight-loss program. The no-breakfast group ate two meals per day and the breakfast group ate three meals per day. After 12-wk, this treatment-by-strata-by-time interaction effect (P less than 0.06) suggests that those who had to make the most substantial changes in eating habits to comply with the program achieved better results.

5 4 3 2 1 0 10 9 8 7 6 Bkfst Breakfast No Bkfst Bkfst No Bkfst No Breakfast

Randomized Experiment of Breakfast and Total Day Energy Intake (Children)

Kral TV, Whiteford LM, Heo M, Faith MS. Effects of eating breakfast compared with skipping breakfast on ratings of appetite and intake at subsequent meals in 8- to 10 y-old children. Am J Clin Nutr. 2011 Feb;93(2):284-91.

Randomized Experiment of Breakfast and Total Day Energy Intake (Young Adults)

David A. Levitsky & Carly Pacanowski. Skipping breakfast results in reduced daily energy intake: Experimental evidence .

Public Health Nutrition

. In press.

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

The Overall Question at the Broadest Level

When one manipulates one aspect of energy intake or expenditure , what is the total effect (if any) on energy stores , and what are the factors and mechanisms influencing that total effect?

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

Do calorie-controlled portion sizes of snacks reduce energy intake?

Stroebele , Ogden, & Hill. Appetite 52 (2009) 793–796 52 (2009) .

Learned

Compensation in Humans

Snack (kcal)

300 250 200 150 100 50 0 Hi-Cal Lo-Cal 1400 1200 1000 800 600 400 200 0 Other food T1 Total T1 Hi-Cal Lo-Cal 1400 1200 1000 800 600 400 200 0 Other Food T2 Total T2 Hi-Cal Lo-Cal

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

The Importance on Non-Surrogate Variables

Faith, Fontaine, Baskin, & Allison.

Psychological Bulletin

. 2007

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

Correlated (non-random) Errors

530 520 510 500 490 480 470 460 450 440 430 420 Measured Self-Reported Intervention Control Harnack L, Himes JH, Anliker J, et al. Intervention-related bias in reporting of food intake by fifth grade children participating in an obesity prevention study. Am J Epidemiol 2004;160:1117 –21.

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

Quasi-Randomization: Holt Adoption Study

0 -0,05 Without Controlling for parental BMI -0,1 -0,15 -0,2 -0,25 -0,3 -0,35 -0,4 Controlling for Parental BMI Biological Children Adopted Children Fontaine KR, Robertson HT, Holst C, Desmond R, Stunkard AJ, Sørensen TI, Allison DB. Is socioeconomic status of the rearing environment causally related to obesity in the offspring? PLoS One. 2011;6(11):e27692.

Roommate Randomization Each extra kg your roommate weighed before freshman year was associated with roughly .05 to .10 kg less weight for you.

Non-Random Assignment & Confounding

The Lanarkshire Milk Experiment: In the spring of 1930, a large scale nutritional was carried out in the schools of Lanarkshire.

controls.

For four months, 5000 children received raw milk, 5000 received pasteurized milk, and 10,000 were DVs: Height & Weight Assignment: Teachers broke from randomization.

Results: No significant differences.

WHAT WENT WRONG?

Student . The Lanarkshire Milk Experiment.

Biometrika

, Vol. 23, No. 3/4 (Dec., 1931), pp. 398-406.

Outline

1. Why we need to study EB.

2. Key Scientific Question.

3. Study duration/time-frame.

4. Selecting the endpoints.

5. Concerns about measurement error.

6. The value of quasi- and natural-experiments.

7. The possibility of true randomization should not be underestimated.

Why think? Why not try the experiment?”

John Hunter, Letter to Edward Jenner, August 2, 1775. A rhetorical slight of hand is sometimes used to dismiss RCTs. Don’t buy it.

Allison DB. Int J Obes 2011 Apr;35(4):464 71. Evidence, discourse and values in obesity-oriented policy: menu labeling as a conversation starter.

Breakfast Revisited: Stay tuned…..

Does Breast Feeding Protect Against Obesity?

an RCT – Results at 6.5 years

16 14 12 10 8 6 4 2 0 B M I W H R * 1 0 T r ic e p s S u b s c a p Experiment al Control

Kramer et al. Am J Clin Nutr. 2007 Dec;86(6):1717-21.

36% 35% 34% Prevalence of BMI > 35 33% 32% 31% 30% 29% 28% Control Low Poverty Voucher Traditional Voucher

To Sum Up: 1. People often react (

compensate

) to a manipulation of one aspect of their energy intake or expenditure by modifying another aspect.

2. The magnitude and even direction of compnesation can vary substantially as a function of the manipulation and circumstances.

3. Long-term compensation responses are not necessarily the same as short-term compensation responses.

4. We cannot yet reliably predict compensation responses and weight changes in response to manipulations of single components of energy balance.

5. Therefore, we must

do the experiments

to find out. 6. And, the experiments can indeed be done.

“…let us take this path through the woods…” Jean-Jacques Rousseau Peavine Falls, Oak Mountain Park, Al From: http://www.encyclopediaofalabama.org/face/Multimedia.jsp?id=m-2898 High Falls, Moss Rock Preserve, Al From: http://farm3.static.flickr.com/2766/4226784012_7a1133a0e9.jpg